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Kidney Week

Abstract: PO1405

Resolving the Kidney's Reaction to Acute Dehydration on the Single-Cell Level

Session Information

Category: Fluid, Electrolyte, and Acid-Base Disorders

  • 901 Fluid, Electrolyte, and Acid-Base Disorders: Basic

Authors

  • Hinze, Christian, Charité-Universtitätsmedizin, Berlin, Berlin, Germany
  • Boivin, Felix, Max Delbrück Center for Molecular Medicine, Berlin, Berlin, Germany
  • Leiz, Janna, Max Delbrück Center for Molecular Medicine, Berlin, Berlin, Germany
  • Karaiskos, Nikos, Berlin Institue for Medical Systems Biology MDC, Berlin, Berlin, Germany
  • Boltengagen, Anastasiya, Berlin Institue for Medical Systems Biology MDC, Berlin, Berlin, Germany
  • Kocks, Christine, Max Delbrück Center for Molecular Medicine, Berlin, Berlin, Germany
  • Rajewsky, Nikolaus, Berlin Institue for Medical Systems Biology MDC, Berlin, Berlin, Germany
  • Schmidt-Ott, Kai M., Charité-Universtitätsmedizin, Berlin, Berlin, Germany
Background

Dehydration is a common clinical finding and frequent among the elderly or patients with chronic diarrhea. Acute kidney injury frequently develops as a result of a fluid deficit. There is growing evidence that recurrent dehydration can cause chronic kidney disease. The kidney’s response to fluid deprivation is incompletely understood. Having a gene expression atlas of the kidney’s reaction to fluid deprivation at single cell resolution might help to understand biological mechanisms but also to identify biomarkers and therapeutic targets.

Methods

We performed single-cell RNA sequencing of dissociated mouse kidneys after 24 hours of water restriction (n=2) and control kidney (n=2). We assigned cell type information based on known marker genes, and systematically analyzed gene expression differences between baseline and water-restricted animals within different cell types. We furthermore applied a computational approach to spatially sort cells based on gene expression similarities to investigate corticomedullary gene expression profiles.

Results

Our data show cell type-specific differential gene expression in all kidney tubule cells with the most prominent response in collecting duct principal cells (CD-PC). Pathways dysregulated in CD-PC included sodium and water reabsorption, immune system modulation and endoplasmatic reticulum (ER) stress. Pathway activation displayed regional cortico-medullary differences.

Conclusion

Fluid deprivation induces regional and cell type-specific responses in kidney cells. Genes and pathways identified by single cell transcriptomics comprise biomarkers and therapeutic targets for dehydration-associated pathologies.